Obesity is currently a major health problem that increases the risk for many diseases, including diabetes, heart disease, hypertension, and some forms of cancer. The growing prevalence of overweight and obese individuals attributed in part to environmental factors such as the abundance of palatable, energy dense foods that are rich in sugar and fat. Laboratory research has documented that high-sugar and high-fat foods promote overeating and obesity in animals. The orosensory properties (flavor) of high-sugar and high-fat foods are clearly attractive to animals and contribute to diet-induced overeating. This attraction is based, in part, on innate taste preferences (e.g., for sweet taste), which appear to involve activation of potent brain reward circuits. Learning also plays an important role in modifying and strengthening food preferences, although much less is known about the neurocircuitry involved. The overall goal of this application is to elucidate the central neurotransmitter systems that support food preference learning and contribute to the appetite for sugar- and fat-rich foods. Research will focus on two types of learning: (a) flavor preferences conditioned by sweet or oily flavors and (b) flavor preferences conditioned by the postingestive actions of sugar and fat. Preliminary findings implicate brain dopamine receptors but not opioid receptors in flavor preference learning produced by sugars. The specific aims of this project are to (1) identify the brain sites (hypothalamic-limbic-cortical) mediating dopamine involvement in sugar-conditioned food preferences;(2) analyze the role of dopamine signaling in fat-conditioned flavor preferences;(3) clarify the involvement of opioid signaling in sugar- and fat-conditioned flavor preferences. This research involves the fields of psychology, neuropharmacology, and neuroscience. It will advance our understanding of the basic mechanisms involved in the development of food preferences and may provide insights into the clinical treatment of overeating and obesity.